The overall objective of the proposed research is the understanding of the mechanisms and conditions of occurrence of free radical reactions between preoxidizing lipids and other biological materials, especially proteins. Specific aims of this research include elucidation of: 1) The nature of reactions leading to production of protein-centered free radicals. 2) The important lipid species (whether lipid hydroperoxides or secondary oxidation products) responsible for the radical transfer. 3) Effects of environmental factors such as water activity and the presence of anti- or pro-oxidants on the transfer of free radicals from peroxidizing lipids to proteins. 4) The relevance of general mechanisms elaborated in model systems to behavior of lipid-protein interactions in more complex tissues. Current studies include peroxidation of liposomes prepared from either phosphatidyl choline, or from lipids extracted from microsomal membrane preparations from fish. Proteins are associated with these liposomes, and their effect on rate of peroxidation, as well as specific biochemical changes in the proteins (loss of enzyme activity, crosslinking, changes in specific amino acid residues) are studied. Effects of disruption of liposomes and/or membranes on sensitivity to oxidation are also determined.